Nimotuzumab combined with gemcitabine versus gemcitabine in K-RAS wild-type locally advanced or metastatic pancreatic cancer: A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial.
Authors: Shukui Qin, Yuxian Bai, Zishu Wang, Zhendong Chen, Ruihua Xu, Jianming Xu, Hongmei Zhang, Jia Chen, Ying Yuan, Tianshu Liu, Lin Yang, Haijun Zhong, Donghui Chen, Lin Shen, Chunyi Hao, Deliang Fu, Ying Cheng, Jianwei Yang, Xian hong Bai, Jin Li
Journal: Journal of Clinical Oncology (2022)

LBA4011 Background: Pancreatic cancer is one of the most lethal malignancies diagnosed at an advanced stage, and current treatment regimens are ineffective, with only 6-8 months of median overall survival (mOS). The present study aims to assess the clinical efficacy and safety of nimotuzumab (anti-EGFR humanized monoclonal antibody) combined with gemcitabine in K-Ras wild-type patients with locally advanced or metastatic pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer were randomized to receive nimotuzumab (400 mg, every one week) followed by gemcitabine (1000 mg/m 2 on days 1, 8, and 15, every four weeks), or placebo plus gemcitabine until progression or unacceptable toxicity. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Use restricted mean survival time (RMST)-Log function to analyze the survival benefits when the proportional hazards assumption is untrue. Results: A total of 92 Chinese patients were randomly assigned to the nimotuzumab- gemcitabine (n = 46) or placebo-gemcitabine group (n = 46). In the full analysis set (FAS, n = 82), the mOS was significantly longer in the nimotuzumab-gemcitabine group (10.9 vs. 8.5 months, p = 0.025 by RMST-Log test, hazard ratio [HR], 0.50, 95% Confidence Interval [CI], 0.06 to 0.94). The one-year survival rate was 43.6% in the nimotuzumab-gemicitabine group vs. 26.8% in the placebo-gemicitabine group, and 13.9% vs. 2.7% at three years. Subgroup analyses showed more survival benefit in patients without treatment of biliary obstruction (11.9 vs. 8.5 months, HR = 0.54, 95%CI 0.33-0.88, p = 0.037) and no surgical history (15.8 vs. 6.0 months, HR = 0.40, 95%CI 0.19-0.84). The median progression-free survival (mPFS) was 4.2 months in the nimotuzumab-gemicitabine group, as compared with 3.6 months in the placebo-gemicitabine group (HR = 0.56; 95% CI, 0.12 to 0.99; p = 0.013 ); Patients without treatment of biliary obstruction had significantly longer PFS (5.5 vs. 3.4 months; p = 0.008 ). No statistical difference in the ORR between the two groups ( p &gt; 0.05). Nimotuzumab was safe and the incidence of adverse events in the nimotuzumab-gemicitabine group is similar to placbo-gemicitabine group. The most common grade 3 TRAEs in Nim-Gem group were neutropenia (11.1%), leukopenia (8.9%) and thrombocytopenia (6.7%). No grade 4 TRAEs. Conclusions: Nimotuzumab combined with gemcitabine increases OS and PFS in patients with K-Ras wild-type locally advanced or metastatic pancreatic cancer, particularly for those without treatment of biliary obstruction. The safety profile of nimotuzumab is similar to placebo. Clinical trial information: 02395016.